With the advancement of research into proliferating and growing undifferentiated stem cells to obtain sufficient numbers of cells, various attempts have been tried to differentiate specific cells to regenerate and replace various injured tissues or organs. In particular, various methods have been advanced for developing adult stem cell differentiation technology which is free from ethical controversy and immune responses using undifferentiated stem cells like mesenchymal stem cells.
In specific differentiation environments, the mesenchymal stem cell in bone marrow has excellent proliferation ability and the potential to differentiate into various tissues such as bone, cartilage, muscle, fat, tendon, ligament, and nerve tissue. Bone/cartilage differentiation is the most advanced area of tissue engineering and differentiation research using stem cells.
In order to differentiate stem cells into bone/cartilage, biochemical differentiation induction methods have been used, in which the composition of culture medium is varied and/or different differentiation induction materials such as a transforming growth factor (TGF), a bone morphogenic protein (BMP), a fibroblast growth factor (FGF), an insulin-like growth factor (IGF), cytokines, and the likes are used. Recently, several research groups have begun to look at stem cell differentiation due to various mechanical factors such as shearing force applied by bodily fluids, compression force applied by various loads or external forces, tensile force, deformation force applied by external forces, elastic variation of an extracellular matrix, and so on.
While no theory about a precise pathway in a process of differentiating stem cells into bone/cartilage cells using mechanical stimulus has been established yet, recent research has revealed that after subjecting stem cells to various stimuli such as hydrostatic pressure, dynamic compression force, cell deformation, tension, hydraulic pressure and flow, electrodynamic force, convection, ultrasonic waves, and so on, protein synthesis and expression of bone/cartilage cell differentiation markers such as Sox9, collagen, GAGs and aggrecan increases, and expression of anti-differentiation factor IL-1 is suppressed.
Since conventional stem cell differentiation experiments using mechanical stimuli involve repeated culturing and differentiation of cells in petridishes, they are costly and laborious. That is, in order to observe variation of stem cells under various mechanical conditions, there is need of a large number of cells, repeated cell culturing, a new culture medium for each experiment, a large laboratory, and an expensive reagent and culture medium.
Therefore, in order to improve manual cell culturing and mechanical stimulus experiments, a new device and system employing various mechanisms and micromachining technologies are needed. In particular, a recently proposed pneumatic pressure-based cell-chip for a stem cell differentiation experiment using mechanical stimulus employs micro electro mechanical system (MEMS) technology to reduce probability of contamination, achieve an ultra-slim and lightweight structure, and enable visual observation using a transparent material.
However, conventional apparatuses for stem cell differentiation experiments using mechanical stimuli still require a separate experiment for each mechanical stimulus, which drives up costs and effort. In addition, they still require manual application of mechanical stimulus and change of culture medium to operate individual chips.